Many cardiac abnormalities in humans can be attributed to defects in the heart during early embryogenesis. Genetic pathways that regulate cardiac development are conserved from insects to humans. The insect heart is a linear tube that is analogous to the linear tube that forms during early stages of vertebrate heart development. The simple structure of the insect heart and the availability of molecular and genetic tools make the heart of the fruit fly an attractive model system for the study of the early events of vertebrate cardiogenesis. Directed cell migration is responsible for bringing specified heart progenitor cells to form the linear heart tube at the midline of the embryo. Interactions of cell surface receptors with molecules in the extracellular matrix are considered to be instrumental for assembly of vascular tissues. However, little is known about what specific guidance cues are participating in this process. Slit is an extracellular matrix molecule that is common to both insects and humans. Slit and its receptor proteins Robo and Robo2 are expressed in the developing Drosophila heart. Severe defects in the assembly of the heart tube are observed in embryos missing the Slit or Robo proteins, indicating that these molecules play an important role in this process. The precise mechanism by which Slit affects heart tube assembly has yet to be determined and is the focus of the research presented in this proposal. [unreadable] [unreadable]